The Medical Defense in Mesothelioma Cases

1. The Medical Defense in Mesothelioma Cases Edward M. Slaughter Hawkins Parnell Thackston & Young LLP 4514 Cole Avenue Dallas, TX 75205

2. Overview • Mesothelioma: The Basics • Stains • Malignancy • Tissue Digestion

3. MESOTHELIOMA: THE BASICS • Pleural • Usually caused by asbestos or some similar fiber, but not always • Peritoneal • Maybe caused by asbestos 50% or less • Pericardial • Rarely caused by asbestos • Testicular mesothelioma • Too uncomfortable to discuss

4. Pleural Mesothelioma

5. Pleural Mesothelioma • Caused by prior radiation therapy at the site • Other fibers • Erionite (which is not just in Turkey) • Taconite • Maybe any fiber that that is biopersistent? • Spontaneous or ideopathic

6. Peritoneal Mesothelioma • Often caused by some other inflammatory process • Be on the lookout for: • Prior hernias • Diverticulitis • Hysterectomies • Anything that leads to chronic inflammation

7. Pericardial and Testicular • If you ever see one we can talk about then.

8. Types of mesothelioma • Epithelial • Sarcomatoid • Biphasic

9. Epithelial

10. Sarcomatoid

11. Biphasic

12. Extremely Rare Diagnosis • Desmoplastic • Really just a rare subtype of sarcomatoid • Hard to diagnose and easily confused with sarcomatoid adenocarcinoma • Benign mesothelial hyperplasia • Reactive process that looks like malignant mesothelioma • Well differentiated papillary mesothelioma • benign

13. Desmoplastic

14. Old men get Mesothelioma • Female mesotheliomas are more often from another cause – maybe 50-50 • Really young people usually don’t have sufficient latency • If the plaintiff is young look for other causes

15. Take Away #1 – Be Suspicious • Mesothelioma in any location other than the pleura (by the lung) is very suspect • Mesothelioma diagnosis with extra words is suspect (wdpm, hyperplasia, etc) • Mesothelioma in young people and women is suspect. • Be suspicious of the diagnosis in these cases.

16. STAINS

17. Stain Limitations • Can’t show if process is malignant or benign • No single stain can definitively diagnose mesothelioma • Glut-1 Caveat

18. Specificity v. Sensitivity EXAMPLE: LeuM1 STAIN • LeuM1 Stain Specific to Adenocarcinoma • LeuM1 Stain Does Not Have High Sensitivity though, because does not react with all adenocarcinoma

19. Other Common Stains • Cytokeratins • Glycoproteins • Calretinin • Thrombomodulin • HBME-1 • Cadherins • TTF-1

20. Stains Used to Diagnose MesotheliomaCK5 - CYTOKERATIN 5/6

21. Stains Used to Diagnose MesotheliomaMESOTHELIN

22. Stains Used to Diagnose MesotheliomaTHROMBOMODULIN

23. Stains Used to Diagnose MesotheliomaHBME-1

24. Stains Used to Diagnose MesotheliomaCALRETININ

25. Stains Used to Diagnose MesotheliomaWT-1

26. Take Away #2 – Stains are just a tool • IHC stains are NEVER enough for a complete diagnosis • They are positive stains and marginally positive stains • No one stain is enough • Stains cannot distinguish between malignant and benign mesotheliomas

27. Diagnosing Malignancy • Invasion • Necrosis • Clinical Correlation • Other factors

28. Stromal Invasion “True stromal invasion is by far the most reliable criterion of mesothelial malignancy” Andrew Churg M.D., et al The Separation of Benign and Malignant Mesothelial Proliferations; The American Journal of Surgical Pathology 24(9):1183

29. Minimal Invasion 06/29/05 - Report of Dr. J.F. Legier …One single slide, 589D4, shows early invasive disease with minimal invasion of fibrous stroma by mesothelial clusters.

30. 6 Days Earlier – Same Pathology 06/23/05 - Report of Dr. J.C. Maddox …based on the clinical history and imaging studies that showed progression of the disease (“malignant mesothelioma on the left with extensive mediastinal invasion…”) … the patient more likely than not had a malignant mesothelioma that caused his death.

31. And Another Opinion 05/21/07 - Report of I. Allen Feingold Despite all of the above hisotpathological and even immunohistochemical evidence against malignancy in this case, it is important to consider the observation of Dr. Robert Viggiano who saw the patientin consultation and follow up…

32. Only Seen 10 Times Q: Okay. And out of those 7- or 800 cases, how many times have you had a difficult diagnosis like this, where you had to compare this sort of a benign, reactive process to a malignant mesothelioma? A: Maybe ten times. Dr. Jacques Legier, pp. 72-73

33. Clinical Correlation • Just fancy talk for “Did the patient seem like a man with mesothelioma?”

34. Necrosis • Is there dead or dying tissue?

35. Other Factors • Read this: Andrew Churg M.D., et al The Separation of Benign and Malignant Mesothelial Proliferations; The American Journal of Surgical Pathology 24(9):1183

36. Take away #3 – Not all Mesotheliomas are Malignant • Stains don’t prove malignancy • Invasion, Necrosis, Clinical Correlation do

38. Tissue Selection • A whole lung is ideal, but not necessary • Autopsy, Pneumonectomy or biopsy • Uninvolved tissue (not the tumor) • The Bigger, The Better • Multiple Sites • But as little as a gram can be enough

39. Results of Fiber Burden Analysis • Evidence of Fiber Type • Amount of Exposure • Evidence of Other Exposures • Helpful with Alternative Exposure Defenses

40. Take Away # 4 Digestion can be valuable • To prove amphibole exposure • To suggest an absence of chrysotile • To prove a dose estimate

41. All 4 Take Aways orThe Big Finale • Be Suspicious of unusual mesotheliomas (extra words, people under 60, women) • Stains are imperfect and don’t prove malignancy - just differentiate between mesothelioma and other processes • Malignancy has to be proven – invasion, necrosis, clinical correlation • Digestion can prove fiber type and dose, but not diagnosis